The LIR is prospectively studying the largest group of patients with the vasculitic syndromes in the world. Clinical, pathophysiologic, immunopathogenic and therapeutic results obtained over the past 14 years have allowed us to design a revised categorization scheme for the vasculitides which has now reached world wide acceptance. We have instituted aggressive chemotherapeutic regimens in several, formerly universally fatal diseases such as Wegener's granulomatosis and have induced cures in 90% or more of these patients. We have now applied these approaches with remarkable success to other of the vasculitic syndromes including systemic vasculitis of the polyarteritis nodosa group, lymphomatoid granulomatosis, isolated CNS vasculitis, Takayasu's arteritis, and the acute vasculitis of Sjogren's syndrome. We have identified a remarkable 100% association of B cell alloantigen MB 3 and Takayasu's arteritis in Americans. These patient populations have been utilized to precisely delineate aberrations of lymphocyte activation and immunoregulation and have served as excellent models for the study of normal human immune function. In addition, the precise effects of various therapeutic regimens, particularly corticosteroids and cytotoxic agents, on human lymphoid cell activation and immunoregulation have been described.